As a common functional group, an amide bond is widely present in natural products such as proteins and synthetic compounds. It is generally believed that the resonance stability of the amide bond makes the amide a weak electrophile (The structure of proteins: two hydrogenbonded helical configurations of the polypeptide chain. Proc. Natl. Acad. Sci. 1951, 37, 205), accordingly, it is difficult to selectively open the C—N bond of the amide by chemical synthesis (Conversion of amides to esters by the nickel-catalysed activation of amide C—N bonds. Nature 2015, 524, 79).
—CONHArF (ArF=p-CF3C6F4) is an excellent amide-guiding group and has a wide range of applications in various types of β-C—H activation reactions, but its disadvantage is that for certain substrates, the guiding group is difficult to remove (Ligand-Enabled β-C—H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary. J. Am. Chem. Soc. 2015, 137, 3338). This greatly limits the further conversion utilization of these C—H activation products, so it is necessary to develop a universal method for removing the guiding group.
Existing methods for removing the guiding group: 1. heating a strong alkali aqueous solution to hydrolyze the amide to a carboxylic acid; 2. heating a strong acid to hydrolyze the amide to a carboxylic acid; 3. adding NaNO2 in a mixed solvent Ac2O/AcOH to obtain a carboxylic acid; 4. obtaining by heating BF3.Et2O in methanol; 5. forming an ester through Hydrolysis by stepwise reaction of LiHMDS/MeOCOCl/MeONa.
For the above method of using BF3.Et2O, the reaction is carried out at 100° C. to achieve alcoholysis of the guiding group, and the method has the disadvantages of expensive reagents, complicated operation and harsh reaction conditions. The remaining methods described above require strong acid or strong base conditions and many functional groups are not stable under these conditions. Moreover, the above methods are all obviously affected by the substrate steric hindrance, and the substrate has a small application range.